U.S. patent number 5,853,749 [Application Number 08/776,481] was granted by the patent office on 1998-12-29 for gel wound dressing.
This patent grant is currently assigned to Scimat Limited. Invention is credited to Tracey Susan Hobbs.
United States Patent |
5,853,749 |
Hobbs |
December 29, 1998 |
**Please see images for:
( Certificate of Correction ) ** |
Gel wound dressing
Abstract
This invention relates to a gel wound dressing material, and to
techniques for preparing and using such a material. The invention
provides a gel wound dressing in which the polymer component
comprises a copolymer of a starch and a monounsaturated carboxylic
acid or an ester or salt thereof, the copolymer being in the form
of particles of which at least 70% by weight have a size of not
more than about 100 um; and water. 1.
Inventors: |
Hobbs; Tracey Susan (Swindon,
GB3) |
Assignee: |
Scimat Limited
(GB3)
|
Family
ID: |
10759378 |
Appl.
No.: |
08/776,481 |
Filed: |
March 31, 1997 |
PCT
Filed: |
July 31, 1995 |
PCT No.: |
PCT/GB95/01804 |
371
Date: |
March 31, 1997 |
102(e)
Date: |
March 31, 1997 |
PCT
Pub. No.: |
WO96/15368 |
PCT
Pub. Date: |
February 15, 1996 |
Foreign Application Priority Data
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|
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Jul 30, 1994 [GB] |
|
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9415739.3 |
|
Current U.S.
Class: |
424/443;
424/78.01; 424/446; 424/445; 424/78.03; 424/78.06 |
Current CPC
Class: |
A61L
26/008 (20130101); A61L 26/0061 (20130101); A61L
26/0014 (20130101); A61L 26/0014 (20130101); C08L
51/02 (20130101) |
Current International
Class: |
A61L
26/00 (20060101); A61K 031/74 (); A61L
015/16 () |
Field of
Search: |
;424/443,78.01,78.03,78.06,445,446,447,449 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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EP 0 100 458 |
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Feb 1984 |
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EP |
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EP 0 157 960 |
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Oct 1985 |
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EP |
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EP 0 169 658 |
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Jan 1986 |
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EP |
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EP 0278 601 |
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Aug 1988 |
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EP |
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EP 0 280 737 |
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Sep 1988 |
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EP |
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EP 0 309 187 |
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Mar 1989 |
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EP |
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0 509 708 |
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Oct 1992 |
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EP |
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1512325 |
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Jan 1978 |
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GB |
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GB 2 048 292 |
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Dec 1980 |
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GB |
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GB 2 083 487 |
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Mar 1982 |
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GB |
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GB 2 156 370 |
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Oct 1985 |
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GB |
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WO91/15368 |
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Oct 1991 |
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WO |
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Other References
Abstract-JP3141229 -"Composition and Drug for Treating Wound", Jun.
1991..
|
Primary Examiner: Page; Thurman K.
Assistant Examiner: Shelborne; Kathryne E.
Attorney, Agent or Firm: Lerner, David, Littenberg, Krumholz
and Mentlik
Claims
We claim:
1. A gel wound dressing which comprises a mixture of:
(a) a water absorbent copolymer of a starch and a mono-unsaturated
carboxylic acid or an ester or salt thereof, the copolymer being in
the form of particles of which at least about 70% by weight have a
size of not more than about 100 .mu.m; and
(b) water.
2. A wound dressing as claimed in claim 1, which includes a
component which reduces the tendency of the dressing to dry out
when exposed to atmosphere.
3. A wound dressing as claimed in claim 2, in which the said
component is a polyol.
4. A wound dressing as claimed in claim 3, in which the said
component comprises propane-1,2-diol.
5. A wound dressing as claimed in claim 2, in which the said
component is present in an amount of at least 100% based on the
weight of the copolymer.
6. A wound dressing as claimed in claim 1, which includes an agent
which inhibits or at least reduces the tendency for bacteria to
colonise on the dressing.
7. A wound dressing as claimed in claim 1, in which the
distribution of the particles of the copolymer is such that at
least about 80% have a particle size of not more than about 100
.mu.m.
8. A wound dressing as claimed in claim 1 in which substantially
all of the carboxyl groups in the copolymer are present as acid
groups, or as salt or ester derivatives of acid groups.
9. A wound dressing as claimed in claim 1, in which the wound
dressing comprises a spreadable gel mixture.
10. A wound dressing as claimed in claim 1, in which the proportion
by weight of copolymer lies in the range from 0.2 to 6%.
11. A wound dressing as claimed in claim 1, in which, in the
formula: ##EQU3## where R is the percentage proportion by weight of
water present in the mixture relative to the total water absorbency
of the copolymer, T is the total water absorbency, x is the
percentage by weight of copolymer and Y is the amount of water in
the mixing stage, R is at least 0.7%.
12. A wound dressing as claimed in claim 11, in which R is not more
than 60%.
13. A wound dressing as claimed in claim 1, which is contained in a
sachet from which the dressing can be extruded by application of
pressure.
14. A wound dressing as claimed in claim 7 in which the
distribution of the particles of the copolymer is such that at
least about 90% have a particle size of not more than about 100
.mu.m.
15. A gel wound dressing contained in a syringe, the gel wound
dressing comprising a mixture of:
(a) a water absorbent polymer of a starch and a monosaturated
carboxylic acid or an ester or salt thereof, the copolymer being in
the form of particles of which at least about 70% by weight have a
size of not more than about 100 .mu.m; and
(b) water.
16. A wound dressing as claimed in claim 15, including a component
which reduces the tendency of the dressing to dry out when exposed
to the atmosphere.
17. A wound dressing as claimed in claim 15, wherein said component
comprises a polyol.
18. A wound dressing as claimed in claim 15, wherein said component
comprises propane-1,2-diol.
19. A wound dressing as claimed in claim 15, wherein said component
is present in an amount of at least 100% based on the weight of the
copolymer.
20. A wound dressing as claimed in claim 15, including an agent
which inhibits or at least reduces the tendency for bacteria to
colonize on the dressing.
21. A wound dressing as claimed in claim 15, wherein the
distribution of the particles of the copolymer is such that at
least about 80% have a particle size of not more than about 100
.mu.m.
22. A wound dressing as claimed in claim 15, wherein substantially
all of the carboxyl groups in the copolymer are present as acid
groups, or as salt or ester derivatives of said acid groups.
23. A wound dressing as claimed in claim 15, wherein said wound
dressing comprises a spreadable gel mixture.
24. A wound dressing as claimed in claim 15, wherein the proportion
by weight of copolymer lies in the range from 0.2 to 6%.
25. A wound dressing as claimed in claim 15, wherein, in the
formula: ##EQU4## where R is the percentage proportion by weight of
water present in the mixture relative to the total water absorbency
of the copolymer, T is the total water absorbency, x is the
percentage by weight of copolymer and Y is the amount of water in
the mixing stage, R is at least 0.7%.
26. A wound dressing as claimed in claim 15, wherein R is not more
than 60% .
Description
This application is a 35 USC 371 of PCT GB95/01804 filed Jul. 31,
1995.
This invention relates to a gel wound dressing material, and to
techniques for preparing and using such a material.
It is desirable to control the condition of a wound to encourage
the healing process by maintaining it sufficiently moist so as to
absorb or to eliminate the formation of dry crusty tissue in the
vicinity of the wound, while also absorbing materials exuded from
the wound, including dead leucocytes, epidermal and dermal cells.
At the same time, it is desirable to prevent access to the wound of
agents, whether bacterial or fungal, which can lead to infection.
Examples of wounds to which these factors are relevant are ulcers,
traumatic and surgical wounds, and burns, and tissue donor
sites.
Traditionally, wounds have been encouraged to heal by placing a
gauze material over the wound. More recently, however, it has been
proposed to apply a gel material over the wound. A suitable gel
material is disclosed in U.S. Pat. No. 4,226,232. It comprises a
hydrolysed copolymer of starch-and an acrylonitrile. The polymer is
prepared in gel form by mixture with water, to an extent which
gives the copolymer an appropriate viscosity which enables it to be
manipulated as a gel, especially when applying it to a wound and
while it is applied to the wound. Modified such materials are
disclosed in U.S. Pat. No. 4,302,369, in which the polymer is
converted to its aluminium salt to increase its ability to absorb
solutions with a high ionic strength.
Appropriate properties for a gel, for use as a wound dressing
include a viscosity that makes the material capable of being
manipulated before administration to a wound and then applied
appropriately over the area of the wound, and an ability to absorb
exudate from the wound. The need to be able to manipulate a gel
material for a wound dressing conveniently has to be balanced with
the ability of the gel to absorb additional liquid; the mixture of
the polymer with water to confer the gel viscosity on the polymer
will result in a reduction of the ability of the polymer to absorb
liquid.
The present invention provides a gel-wound dressing in which the
polymer component comprises a copolymer of a starch and a
monounsaturated carboxylic acid or an ester or salt thereof.
Accordingly, in one aspect, the invention provides a gel wound
dressing which comprises:
(a) a water absorbent copolymer of a starch and a mono-unsaturated
carboxylic acid or an ester or salt thereof; and
(b) water.
The dressing material may further comprise a preservative or other
additive.
The dressing of the invention has the advantage that it can be
provided as a gel, and therefore be manipulated conveniently before
application to a wound and while it is so applied, with an ability
to absorb fluids which can be at least comparable with gel wound
dressings based on other polymer systems. The dressing can also
provide appropriate moisture levels to minimise the risk of a wound
drying out during the healing process, which can itself give rise
to complications in the healing process in terms of the formation
of crusty tissue. The dressing material of the invention can be
made with a viscosity which is at least about 100 kcps, preferably
at least about 125 kcps, for example at least about 160 kcps. The
viscosity can be arranged to be not more than about 300 kcps, more
preferably not more than about 275 kcps, for example not more than
about 250 kcps. The viscosity of the dressing material is measured
on a Brookfield RVF viscometer with a helipath stand, using a T-bar
D spindle at 4 rpm.
The viscosities referred to above can be attained according to the
present invention while maintaining a high ability to absorb exuded
materials from the wound as can be demonstrated by means of a
saline absorption test. That test comprises dispersing 2 g of the
dressing material in 20 ml of 0.9% aqueous NaCl solution. The
dispersion is decanted into a 50 ml measuring cylinder. Once the
dispersion has settled, the position of the phase separation is
noted from which the fluid absorption capacity can be calculated.
It has been found that the dressing material of the invention can
be made with a viscosity within the limits mentioned above, with a
saline absorption of at least about 200 ml of the solution per 100
g of the wound dressing, preferably at least about 250 ml.100
g.sup.-1, more preferably at least about 300 ml.100 g.sup.-1. The
absorption characteristics of the dressing material have been found
to be enhanced as a result of a sterilisation step in its
preparation which involves exposing the material to heat and
pressure. The viscosity that can be obtained in the material of the
wound dressing material of the invention means that the material is
capable of being manipulated conveniently over the area of the
wound that is to be treated using the material. It also facilitates
removal of the material from its packaging. In addition to
facilitating manipulation, a relatively low viscosity can enable
the tackiness of the material to be maintained relatively low,
which reduces damage to the wound when the dressing is removed.
Control of the viscosity is one means of measurement which may be
used to obtain a required ratio between copolymer and water in the
gel mixture. However, other means may be adopted, to achieve
desired water-absorption properties of the gel mixture, which
effectively comprises required provision of a suitable "spreadable
gel". This can range between "highly mobile" at one extreme to
"very stiff" at the other extreme, and which can be obtained by
variation of the proportion by weight of copolymer in the gel
mixture between about 0.2% to about 6%. The particular weight
proportion which may be selected can depend on the particular means
adopted to dispense the gel mixture, with e.g. a highly mobile gel
being suitable for introduction into a deep wound by a syringe, and
a stiffer gel being suitable for extrusion e.g. from a squeezable
sachet so as to be readily spread over the wound area.
In one preferred arrangement, the gel mixture may be stored in a
squeezable sachet, and therefore the required properties of the gel
mixture will be such that it can be readily be squeezed from the
sachet, and to be readily spread over the wound area.
The gel wound dressing of the invention has been found to be
capable of providing suitable absorption characteristics, in
particular towards solutions which are high in ionic strength,
without any need to include aluminium ions. This can represent a
significant advantage, in particular in situations in which the
presence of aluminium ions can give rise to clinical
complications.
Preferably, the gel wound dressing is formed from a mixture of
particles of the copolymer and water, in which the distribution of
particles is such that at least about 70% by weight, more
preferably at least about 80%, especially at least about 90%, have
a particle size of not more than about 100 .mu.m. Preferably, the
gel wound dressing is formed from a mixture of particles of the
copolymer and water, in which the distribution of particles is such
that at least about 60% by weight, more preferably at least about
70%, especially at least about 85%, have a particle size of not
more than about 75 .mu.m. Preferably, the distribution of particles
is such that not more than about 10% by weight, more preferably not
more than about 6%, have a particle size greater than about 100
.mu.m. The particle size distribution can be determined using
sieves with known mesh sizes, as is known.
It has been found that the use of particles of the copolymer whose
size satisfies some or all of these conditions gives rise to
materials with viscosities which make the copolymer suitable for
use in the treatment of wounds, with the characteristics of a gel.
The use of particles of the polymer with a size within these ranges
has the advantage of making the material smoother without a
granular texture. The smooth texture makes the material easier to
spread appropriately over a wound that is to be treated. Also the
gel usually will be clear i.e. transparent, so that the wound can
be observed while the dressing is being applied.
Preferably, the gel wound dressing of the invention includes a
component which reduces its tendency to dry out. This component may
also act as a preservative. Examples of suitable materials include
polyols, such as propane-1,2-diol and glycerol, or a mixture
thereof. Preferably, the polyol component is present in the
composition in an amount of at least about 100% by weight based on
the weight of the copolymer, more preferably at least about 200%,
especially at least about 300%, for example about 400%, and with
advantage even up to 600%.
Preferably, the gel wound dressing of the invention includes at
least one other active component. For example, the dressing might
include an agent which inhibits or at least reduces the tendency
for bacteria to colonise on the dressing. An example of a suitable
such agent is a polyol such as propane-1,2-diol.
Examples of other active components that might be included in the
dressing include anaesthetic agents, hormonal compounds and
lubricants, enzyme-containing compositions, antibiotics (such as
metronidazole), collagen materials, cytokines (such as platelet
derived growth factor, insulin-dependent growth factor, and
transforming factored placentile growth factor), and elastin
(preferably with fibrin and fibrinogen).
The copolymer used in the dressing is produced by reaction of a
starch with a monoethylenically unsaturated carboxylic acid, or an
ester or salt of such an acid. Examples of suitable components for
the copolymer, together with the starch, include acrylic acid,
methacrylic acid, lower carboxyl (C.sub.1 to C.sub.4) esters
thereof and salts such as with elements of Groups I and II or
ammonia. It is preferred that substantially all of the carboxyl
groups in the copolymer are present as acid groups, or as salt or
ester derivatives of acid groups.
A particularly preferred copolymer comprises at least about 50%,
preferably at least about 70%, more preferably at least about 85%,
for example at least about 95%, of a salt of a starch grafted
polyacrylate. Preferred salts include toe sodium salt.
The copolymerisation reaction between the starch and the acrylate
component can be initiated by means of irradiation, for example
using an electron beam, .gamma.-radiation such as from a Co.sup.60
source, or ultraviolet radiation. The reaction can also be
initiated by means of a chemical initiator such as benzoyl
peroxide, hydrogen peroxide or a salt such as a ceric salt.
Examples of suitable copolymers for use in the gel wound dressing
of the invention are disclosed in GB-1512325. Subject matter
disclosed in that document is incorporated in the specification of
this application by this reference. The document discloses a water
absorbing resin which comprises a copolymer of starch and a water
soluble monomer such as acrylic acid or a derivative thereof. The
resin is crosslinked as a result of a reaction with a crosslinking
agent such as polyesters of unsaturated mono- or polycarboxylic
acids with polyols (for example an ester of di-methacrylic acid
with ethylene glycol). The resin is said to be suitable for
absorbing fluids such as blood and urine, for example in diapers,
sanitary towels and disposable dustcloths for kitchens. The
disclosed resin can be applied in the form of a powder, in an
aqueous dispersion, or by immersion of a substrate in a solution of
the resin. The resin is said to be particularly suitable for use in
diapers and sanitary towels.
The copolymer used in the dressing of the invention will generally
be crosslinked, so as to confer appropriate gel-like properties and
viscosity on the dressing material. The crosslinks will preferably
be internal crosslinks. It has been found that the use of a polymer
which is crosslinked in this way gives rise to a smoother dressing
material, which has advantages in use for example in terms of its
ability to be spread.
The starch used to form the copolymer may be a natural starch such
as potato starch, rice starch, tapioca starch or corn starch, or a
modified or processed starch such as .alpha.-starch, dextrine and
oxidised starch. Natural starches are particularly preferred.
The ratio by weight of the starch to the acid derivative component
of the copolymer is preferably at least about 1, more preferably at
least about 2, especially at least about 5, for example at least
about 10. The ratio is preferably not more than about 10.sup.4,
more preferably not more than about 10.sup.3, especially not more
than about 100.
Suitable starch acrylate copolymers for use in the wound dressing
of the invention are available from Hoechst Celanese under the
trade mark SANWET COS-915.
Preferably, the water that is present in the wound dressing gel is
not more than about 60% of the total water absorbency of the
copolymer, more preferably not more than about 5%, for example not
more than about 3%.
The water absorbency of the copolymer is determined by immersing in
deionised water a known weight of the gel (1 to 2 g) made to the
exemplified formulation, contained in a sealed bag of a hydrophilic
polypropylene based non-woven fabric available from Scimat Limited
under the trade mark SCIMAT 700/13, and recording its weight change
after 24 hours.
Prior to weighing, the surface of the bag is blotted to remove
excess water and an empty bag is used as a control.
The total absorbency of the resin, measured in ml.g.sup.-1, is
calculated as follows: ##EQU1## However, the total water absorbency
(T) can be difficult to measure in practice (due to variation
between different batches of material), but tests carried out to
date give the following desired parameters, wherein carrying out
measurements for values from 900 to 1300 ml/g for pure water:
##EQU2## in which R is the percentage proportion by weight of water
present in the gel mixture relative to the total water absorbency
of the copolymer in the gel mixture; T is the total water
absorbency; x is the percentage by weight of copolymer in the
copolymer/water gel mixture, and Y=amount of water added in the
mixing stage.
For values of x=0.2 and T=900 and 1300 and Y=99.8, the values of R
were found to be 55.4 and 38.4 respectively.
For value of x=6, and values of T=900 and T=1300 and Y=94, the
values of R were found to be 1.74 and 1.21 respectively.
The value of x=0.2 gives a gel mixture which is very runny, or
"highly mobile" as indicated earlier, whereas the value x=6.0 gives
a gel mixture which is very stiff. These two values of x determine
the range within which a suitable spreadable gel can be derived, to
suit particular requirements. Therefore, suitable variation of the
weight proportions of copolymer and water in the gel mixture may be
selected, by experiment, within the range, to provide spreadable
gel mixtures suitable for different requirements.
In a preferred example, which contains 3.5 parts copolymer and 75.5
parts water, then when T=900, R=2.4; and when T=1300, R=1.66, and
Y=75.5.
Accordingly, in a particularly preferred range of proportion by
weight of copolymer to water in a gel mixture of a gel wound
dressing according to the invention, the relative proportion of
water that is present in a particular sample, compared with the
total water absorbency of the copolymer in the sample, lies in a
range having a minimum value of up to 1.0%. The upper limit to the
preferred range will be determined by experiment, but may go up to
as high a value as R=60%.
If desired, for certain circumstances it may be advantageous to
introduce substantial amounts of preservative e.g. a polyol into
the gel mixture, (which replaces the amount of water required in
the formulation of the gel), and this can then result in a lower
value of R. By way of example, in a gel mixture of 3% polymer, 69%
polyol, and 28% water, the value of R is reduced to 0.7. The
invention therefore includes the possibility of including weight
proportions in the gel mixture of polymer, preservative, and water
such that R can be less than 1.0%, and down to at least 0.7%.
The gel dressing will generally be applied to a wound in a layer of
thickness at least about 2 mm, preferably at least about 4 mm, for
example at least about 5 mm. A dressing applied to certain wounds
with this thickness can be left in situ for as much as seven days
or more.
The dressing of the invention can be administered in a sachet from
which it can be extruded through an opening, formed for example by
means of a knife, by the application of pressure to the sachet.
The dressing can conveniently be administered in a syringe, from
which it can be extruded in a controlled manner directly onto a
wound so that it is appropriately located to ensure that the
wetness of the wound is controlled.
The dressing can be administered in a porous container such as a
pouch or sachet made of a material that is suitably porous to the
fluids to be absorbed by the dressing when in place on the wound.
Examples of materials that might be suitable for the sachet or
pouch include paper based materials and organic materials such as
polyamides and polyesters, especially in the form of a non-woven
sheet.
The wound dressing of the invention can conveniently be applied
directly to a wound. It is envisaged that, in most circumstances,
the dressing will be changed after a period of, perhaps, hours or
days, according to the condition of the wound, for example about 2
to 3 days (although shorter periods can be appropriate under
certain conditions, for example when the amount of material exuding
from the wound is high). When the dressing is to be changed, the
gel-like characteristics of the dressing material facilitate its
removal from the wound, and which may be assisted by irrigation,
for example using a sterile saline solution.
It will generally be appropriate for a secondary dressing to be
applied over the gel wound dressing, to retain it in place on a
wound and to provide a degree of physical protection for the gel
dressing. The nature of the secondary dressing will depend on the
characteristics of the wound. For example, if the wound has eschar
(dry crusty tissue) associated with it, a moisture vapour permeable
dressing will be appropriate. If the wound is malodorous, an
activated carbon dressing can be appropriate.
An appropriate secondary dressing can preferably exclude bacteria
from the wound, retain the dressing material in place on the wound,
and permit exchange of moisture with the atmosphere. Preferably,
the dressing is transparent so that the wound can be inspected.
Suitable secondary dressings are sold under the trade marks OPSITE
and TEGADERM.
The invention also provides a method of making a gel wound dressing
material, which comprises mixing a water absorbent copolymer of a
starch and a monounsaturated carboxylic acid or an ester or salt
thereof with a quantity of water, the proportions of the copolymer
and water being such that the resulting mixture has gel
properties.
Preferably, the method includes the step of sterilising the gel
wound dressing, for example by means of a heating step, optionally
under pressure, or by irradiation if the materials of the dressing
are not affected adversely by irradiation. Unexpectedly the saline
absorbency capacity of the sterilised gel is greater than that
before sterilisation.
The invention further provides a method of treating a wound which
includes the step of applying a gel wound dressing of the type
discussed above.
An example of a gel wound dressing will now be described. The
dressing was made from a starch acrylate copolymer sold under the
trade mark SANWET COS-915. It is supplied by Hoechst Celanese.
Typically it has a particle size distribution as follows:
* * * * *